Advances in the Development of Anticancer HSP-based Vaccines

Author(s): Alexey V. Baldin, Andrey A. Zamyatnin Jr, Alexandr V. Bazhin, Wan-Hai Xu, Lyudmila V. Savvateeva*.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 3 , 2019

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Current advances in cancer treatment are based on the recent discoveries of molecular mechanisms of tumour maintenance. It was shown that heat shock proteins (HSPs) play a crucial role in the development of immune response against tumours. Thus, HSPs represent multifunctional agents not only with chaperone functions, but also possessing immunomodulatory properties. These properties are exploited for the development of HSP-based anticancer vaccines aimed to induce cytotoxic responses against tumours. To date, a number of strategies have been suggested to facilitate HSP-based vaccine production and to increase its effectiveness. The present review focuses on the current trend for the development of HSPbased vaccines aimed at inducing strong immunological tumour-specific responses against cancer cells of distinct etiology and localization.

Keywords: Heat shock proteins, chaperones, immune response, anticancer vaccine, tumor-associated antigens, tumor- specific antigens.

Ellis, R.J. Protein misassembly: Macromolecular crowding and molecular chaperones. Adv. Exp. Med. Biol., 2007, 594, 1-13.
Jee, H. Size dependent classification of heat shock proteins: A mini-review. J. Exerc. Rehabil., 2016, 12(4), 255-259.
Kampinga, H.H.; Hageman, J.; Vos, M.J.; Kubota, H.; Tanguay, R.M.; Bruford, E.A.; Cheetham, M.E.; Chen, B.; Hightower, L.E. Guidelines for the nomenclature of the human heat shock proteins. Cell Stress Chaperones, 2009, 14(1), 105-111.
Rüdiger, S.; Buchberger, A.; Bukau, B. Interaction of Hsp70 chaperones with substrates. Nat. Struct. Biol., 1997, 4(5), 342-349.
Vogel, M.; Mayer, M.P.; Bukau, B. Allosteric regulation of Hsp70 chaperones involves a conserved interdomain linker. J. Biol. Chem., 2006, 281(50), 38705-38711.
Thériault, J.R.; Adachi, H.; Calderwood, S.K. Role of scavenger receptors in the binding and internalization of heat shock protein 70. J. Immunol., 2006, 177(12), 8604-8611.
Lancaster, G.I.; Febbraio, M.A. Exosome-dependent trafficking of HSP70: A novel secretory pathway for cellular stress proteins. J. Biol. Chem., 2005, 280(24), 23349-23355.
De Maio, A.; Vazquez, D. Extracellular heat shock proteins: A new location, a new function. Shock, 2013, 40(4), 239-246.
Ghosh, J.G.; Houck, S.A.; Clark, J.I. Interactive domains in the molecular chaperone human alphaB crystallin modulate microtubule assembly and disassembly. PLoS One, 2007, 2(6), e498.
Melkani, G.C.; Cammarato, A.; Bernstein, S.I. alphaB-crystallin maintains skeletal muscle myosin enzymatic activity and prevents its aggregation under heat-shock stress. J. Mol. Biol., 2006, 358(3), 635-645.
Rosenfeld, G.E.; Mercer, E.J.; Mason, C.E.; Evans, T. Small heat shock proteins Hspb7 and Hspb12 regulate early steps of cardiac morphogenesis. Dev. Biol., 2013, 381(2), 389-400.
Juo, L.Y.; Liao, W.C.; Shih, Y.L.; Yang, B.Y.; Liu, A.B.; Yan, Y.T. HSPB7 interacts with dimerized FLNC and its absence results in progressive myopathy in skeletal muscles. J. Cell Sci., 2016, 129(8), 1661-1670.
Hennessy, F.; Nicoll, W.S.; Zimmermann, R.; Cheetham, M.E.; Blatch, G.L. Function and chemotypes of human Hsp70 chaperones. Curr. Top. Med. Chem., 2016, 16(25), 2812-2828.
Gupta, S.; Knowlton, A.A. HSP60, Bax, apoptosis and the heart. J. Cell. Mol. Med., 2005, 9(1), 51-58.
Shrestha, L.; Young, J.C. Function and Chemotypes of Human Hsp70 Chaperones. Curr. Top. Med. Chem., 2016, 16(25), 2812-2828.
Jackson, S.E. Hsp90: Structure and function. Top. Curr. Chem., 2013, 328, 155-240.
Easton, D.P.; Kaneko, Y.; Subjeck, J.R. The hsp110 and Grp1 70 stress proteins: newly recognized relatives of the Hsp70s. Cell Stress Chaperones, 2000, 5(4), 276-290.
Belli, F.; Testori, A.; Rivoltini, L.; Maio, M.; Andreola, G.; Sertoli, M.R.; Gallino, G.; Piris, A.; Cattelan, A.; Lazzari, I.; Carrabba, M.; Scita, G.; Santantonio, C.; Pilla, L.; Tragni, G.; Lombardo, C.; Arienti, F.; Marchianò, A.; Queirolo, P.; Bertolini, F.; Cova, A.; Lamaj, E.; Ascani, L.; Camerini, R.; Corsi, M.; Cascinelli, N.; Lewis, J.J.; Srivastava, P.; Parmiani, G. Vaccination of metastatic melanoma patients with autologous tumor-derived heat shock protein gp96-peptide complexes: Clinical and immunologic findings. J. Clin. Oncol., 2002, 20(20), 4169-4180.
Rad-Malekshahi, M.; Fransen, M.F.; Krawczyk, M.; Mansourian, M.; Bourajjaj, M.; Chen, J.; Ossendorp, F.; Hennink, W.E.; Mastrobattista, E.; Amidi, M. Self-Assembling Peptide Epitopes as Novel Platform for Anticancer Vaccination. Mol. Pharm., 2017, 14(5), 1482-1493.
Udono, H.; Srivastava, P.K. Heat shock protein 70-associated peptides elicit specific cancer immunity. J. Exp. Med., 1993, 178(4), 1391-1396.
Blachere, N.E.; Li, Z.; Chandawarkar, R.Y.; Suto, R.; Jaikaria, N.S.; Basu, S.; Udono, H.; Srivastava, P.K. Heat shock protein-peptide complexes, reconstituted in vitro, elicit peptide-specific cytotoxic T lymphocyte response and tumor immunity. J. Exp. Med., 1997, 186(8), 1315-1322.
Tang, D.; Khaleque, M.A.; Jones, E.L.; Theriault, J.R.; Li, C.; Wong, W.H.; Stevenson, M.A.; Calderwood, S.K. Expression of heat shock proteins and heat shock protein messenger ribonucleic acid in human prostate carcinoma in vitro and in tumors in vivo. Cell Stress Chaperones, 2005, 10(1), 46-58.
Banerjee, S.; Lin, C.F.; Skinner, K.A.; Schiffhauer, L.M.; Peacock, J.; Hicks, D.G.; Redmond, E.M.; Morrow, D.; Huston, A.; Shayne, M.; Langstein, H.N.; Miller-Graziano, C.L.; Strickland, J.; O’Donoghue, L.; De, A.K. Heat shock protein 27 differentiates tolerogenic macrophages that may support human breast cancer progression. Cancer Res., 2011, 71(2), 318-327.
Calderwood, S.K.; Gong, J. Heat Shock Proteins Promote Cancer: It’s a Protection Racket. Trends Biochem. Sci., 2016, 41(4), 311-323.
Stocki, P.; Morris, N.J.; Preisinger, C.; Wang, X.N.; Kolch, W.; Multhoff, G.; Dickinson, A.M. Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA). Cell Stress Chaperones, 2010, 15(5), 729-741.
Basu, S.; Binder, R.J.; Suto, R.; Anderson, K.M.; Srivastava, P.K. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int. Immunol., 2000, 12(11), 1539-1546.
Mambula, S.S.; Calderwood, S.K. Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes. J. Immunol., 2006, 177(11), 7849-7857.
Mambula, S.S.; Calderwood, S.K. Heat induced release of Hsp70 from prostate carcinoma cells involves both active secretion and passive release from necrotic cells. Int. J. Hyperthermia, 2006, 22(7), 575-585.
Vega, V.L.; Rodríguez-Silva, M.; Frey, T.; Gehrmann, M.; Diaz, J.C.; Steinem, C.; Multhoff, G.; Arispe, N.; De Maio, A. Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J. Immunol., 2008, 180(6), 4299-4307.
Borges, T.J.; Wieten, L.; van Herwijnen, M.J.; Broere, F.; van der Zee, R.; Bonorino, C.; van Eden, W. The anti-inflammatory mechanisms of Hsp70. Front. Immunol., 2012, 3, 95.
Pockley, A.G.; Muthana, M.; Calderwood, S.K. The dual immunoregulatory roles of stress proteins. Trends Biochem. Sci., 2008, 33(2), 71-79.
Luo, X.; Zuo, X.; Zhou, Y.; Zhang, B.; Shi, Y.; Liu, M.; Wang, K.; McMillian, D.R.; Xiao, X. Extracellular heat shock protein 70 inhibits tumour necrosis factor-alpha induced proinflammatory mediator production in fibroblast-like synoviocytes. Arthritis Res. Ther., 2008, 10(2), R41.
Stocki, P.; Wang, X.N.; Dickinson, A.M. Inducible heat shock protein 70 reduces T cell responses and stimulatory capacity of monocyte-derived dendritic cells. J. Biol. Chem., 2012, 287(15), 12387-12394.
Miller-Graziano, C.L.; De, A.; Laudanski, K.; Herrmann, T.; Bandyopadhyay, S. HSP27: An anti-inflammatory and immunomodulatory stress protein acting to dampen immune function. Novartis Found. Symp., 2008, 291, 196-208.
Rayner, K.; Chen, Y.X.; McNulty, M.; Simard, T.; Zhao, X.; Wells, D.J.; de Belleroche, J.; O’Brien, E.R. Extracellular re-lease of the atheroprotective heat shock protein 27 is mediat-ed by estrogen and competitively inhibits acLDL binding to scavenger receptor-A. Circ. Res; , 2008, 103, . (2),133-141
De, A.K.; Kodys, K.M.; Yeh, B.S.; Miller-Graziano, C. Exaggerated human monocyte IL-10 concomitant to minimal TNF-alpha induction by heat-shock protein 27 (Hsp27) suggests Hsp27 is primarily an antiinflammatory stimulus. J. Immunol., 2000, 165(7), 3951-3958.
de Kleer, I.; Vercoulen, Y.; Klein, M.; Meerding, J.; Albani, S.; van der Zee, R.; Sawitzki, B.; Hamann, A.; Kuis, W.; Prakken, B. CD30 discriminates heat shock protein 60-induced FOXP3+ CD4+ T cells with a regulatory phenotype. J. Immunol., 2010, 185(4), 2071-2079.
Aalberse, J.A.; Kapitein, B.; de Roock, S.; Klein, M.R.; de Jager, W.; van der Zee, R.; Hoekstra, M.O.; van Wijk, F.; Prakken, B.J. Cord blood CD4+ T cells respond to self heat shock protein 60 (HSP60). PLoS One, 2011, 6(9), e24119.
Cohen-Sfady, M.; Nussbaum, G.; Pevsner-Fischer, M.; Mor, F.; Carmi, P.; Zanin-Zhorov, A.; Lider, O.; Cohen, I.R. Heat shock protein 60 activates B cells via the TLR4-MyD88 pathway. J. Immunol., 2005, 175(6), 3594-3602.
Ueki, K.; Tabeta, K.; Yoshie, H.; Yamazaki, K. Self-heat shock protein 60 induces tumour necrosis factor-alpha in monocyte-derived macrophage: possible role in chronic inflammatory periodontal disease. Clin. Exp. Immunol., 2002, 127(1), 72-77.
Gastpar, R.; Gehrmann, M.; Bausero, M.A.; Asea, A.; Gross, C.; Schroeder, J.A.; Multhoff, G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res., 2005, 65(12), 5238-5247.
Gehrmann, M.; Marienhagen, J.; Eichholtz-Wirth, H.; Fritz, E.; Ellwart, J.; Jäättelä, M.; Zilch, T.; Multhoff, G. Dual function of membrane-bound heat shock protein 70 (Hsp70), Bag-4, and Hsp40: protection against radiation-induced effects and target structure for natural killer cells. Cell Death Differ., 2005, 12(1), 38-51.
Bausinger, H.; Lipsker, D.; Ziylan, U.; Manié, S.; Briand, J.P.; Cazenave, J.P.; Muller, S.; Haeuw, J.F.; Ravanat, C.; de la Salle, H.; Hanau, D. Endotoxin-free heat-shock protein 70 fails to induce APC activation. Eur. J. Immunol., 2002, 32(12), 3708-3713.
Facciponte, J.G.; Wang, X.Y.; Subjeck, J.R. Hsp110 and Grp170, members of the Hsp70 superfamily, bind to scavenger receptor-A and scavenger receptor expressed by endothelial cells-I. Eur. J. Immunol., 2007, 37(8), 2268-2279.
Tsai, Y.P.; Yang, M.H.; Huang, C.H.; Chang, S.Y.; Chen, P.M.; Liu, C.J.; Teng, S.C.; Wu, K.J. Interaction between HSP60 and beta-catenin promotes metastasis. Carcinogenesis, 2009, 30(6), 1049-1057.
Chalmin, F.; Ladoire, S.; Mignot, G.; Vincent, J.; Bruchard, M.; Remy-Martin, J.P.; Boireau, W.; Rouleau, A.; Simon, B.; Lanneau, D.; De Thonel, A.; Multhoff, G.; Hamman, A.; Martin, F.; Chauffert, B.; Solary, E.; Zitvogel, L.; Garrido, C.; Ryffel, B.; Borg, C.; Apetoh, L.; Rébé, C.; Ghiringhelli, F. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J. Clin. Invest., 2010, 120(2), 457-471.
Marigo, I.; Dolcetti, L.; Serafini, P.; Zanovello, P.; Bronte, V. Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol. Rev., 2008, 222, 162-179.
Srivastava, P.K.; DeLeo, A.B.; Old, L.J. Tumor rejection antigens of chemically induced sarcomas of inbred mice. Proc. Natl. Acad. Sci. USA, 1986, 83(10), 3407-3411.
Maki, R.G.; Old, L.J.; Srivastava, P.K. Human homologue of murine tumor rejection antigen gp96: 5′-regulatory and coding regions and relationship to stress-induced proteins. Proc. Natl. Acad. Sci. USA, 1990, 87(15), 5658-5662.
Blachere, N.E.; Udono, H.; Janetzki, S.; Li, Z.; Heike, M.; Srivastava, P.K. Heat shock protein vaccines against cancer. J. Immunother. Emphasis Tumor Immunol., 1993, 14(4), 352-356.
Ishii, T.; Udono, H.; Yamano, T.; Ohta, H.; Uenaka, A.; Ono, T.; Hizuta, A.; Tanaka, N.; Srivastava, P.K.; Nakayama, E. Isolation of MHC class I-restricted tumor antigen peptide and its precursors associated with heat shock proteins hsp70, hsp90, and gp96. J. Immunol., 1999, 162(3), 1303-1309.
Tamura, Y.; Peng, P.; Liu, K.; Daou, M.; Srivastava, P.K. Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science, 1997, 278(5335), 117-120.
Noessner, E.; Gastpar, R.; Milani, V.; Brandl, A.; Hutzler, P.J.; Kuppner, M.C.; Roos, M.; Kremmer, E.; Asea, A.; Calderwood, S.K.; Issels, R.D. Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J. Immunol., 2002, 169(10), 5424-5432.
Mazzaferro, V.; Coppa, J.; Carrabba, M.G.; Rivoltini, L.; Schiavo, M.; Regalia, E.; Mariani, L.; Camerini, T.; Marchi-ano, A.; Andreola, S.; Camerini, R.; Corsi, M.; Lewis, J.J.; Srivastava, P.K.; Parmiani, G. Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer. Clin. Cancer Res., 2003, 9(9), 3235-3245.
Reitsma, D.J.; Combest, A.J. Challenges in the development of an autologous heat shock protein based anti-tumor vaccine. Hum. Vaccin. Immunother., 2012, 8(8), 1152-1155.
Randazzo, M.; Terness, P.; Opelz, G.; Kleist, C. Active-specific immunotherapy of human cancers with the heat shock protein Gp96-revisited. Int. J. Cancer, 2012, 130(10), 2219-2231.
Gancberg, D.; Di Leo, A.; Cardoso, F.; Rouas, G.; Pedrocchi, M.; Paesmans, M.; Verhest, A.; Bernard-Marty, C.; Piccart, M.J.; Larsimont, D. Comparison of HER-2 status between primary breast cancer and corresponding distant metastatic sites. Ann. Oncol., 2002, 13(7), 1036-1043.
Ito, H.; Hatori, M.; Kinugasa, Y.; Irie, T.; Tachikawa, T.; Nagumo, M. Comparison of the expression profile of metastasis-associated genes between primary and circulating cancer cells in oral squamous cell carcinoma. Anticancer Res., 2003, 23(2B), 1425-1431.
Flynn, G.C.; Chappell, T.G.; Rothman, J.E. Peptide binding and release by proteins implicated as catalysts of protein assembly. Science, 1989, 245(4916), 385-390.
Savvateeva, L.V.; Schwartz, A.M.; Gorshkova, L.B.; Gorokhovets, N.V.; Makarov, V.A.; Reddy, V.P.; Aliev, G.; Zamyatnin, A.A., Jr Prophylactic admission of an in vitro reconstructed complexes of human recombinant heat shock proteins and melanoma antigenic peptides activates anti-melanoma responses in mice. Curr. Mol. Med., 2015, 15(5), 462-468.
Graziano, D.F.; Finn, O.J. Tumor antigens and tumor antigen discovery. Cancer Treat. Res., 2005, 123, 89-111.
Coulie, P.G.; Van den Eynde, B.J.; van der Bruggen, P.; Boon, T. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat. Rev. Cancer, 2014, 14(2), 135-146.
Huo, W.; Ye, J.; Liu, R.; Chen, J.; Li, Q. Vaccination with a chaperone complex based on PSCA and GRP170 adjuvant enhances the CTL response and inhibits the tumor growth in mice. Vaccine, 2010, 28(38), 6333-6337.
Wang, X.J.; Gu, K.; Xu, J.S.; Li, M.H.; Cao, R.Y.; Wu, J.; Li, T.M.; Liu, J.J. Immunization with a recombinant GnRH vaccine fused to heat shock protein 65 inhibits mammary tumor growth in vivo. Cancer immunology, immunotherapy. CII, 2010, 59(12), 1859-1866.
Staib, F.; Distler, M.; Bethke, K.; Schmitt, U.; Galle, P.R.; Heike, M. Cross-presentation of human melanoma peptide antigen MART-1 to CTLs from in vitro reconstituted gp96/MART-1 complexes. Cancer Immun., 2004, 4, 3.
Hu, T.; Li, D.; Zhao, Y. Development of the hsp110-heparanase vaccine to enhance antitumor immunity using the chaperoning properties of hsp110. Mol. Immunol., 2009, 47(2-3), 298-301.
Zhou, L.; Zhu, T.; Ye, X.; Yang, L.; Wang, B.; Liang, X.; Lu, L.; Tsao, Y.P.; Chen, S.L.; Li, J.; Xiao, X. Long-term protection against human papillomavirus e7-positive tumor by a single vaccination of adeno-associated virus vectors encoding a fusion protein of inactivated e7 of human papillomavirus 16/18 and heat shock protein 70. Hum. Gene Ther., 2010, 21(1), 109-119.
Ren, F.; Xu, Y.; Mao, L.; Ou, R.; Ding, Z.; Zhang, X.; Tang, J.; Li, B.; Jia, Z.; Tian, Z.; Ni, B.; Wu, Y. Heat shock protein 110 improves the antitumor effects of the cytotoxic T lymphocyte epitope E7(49-57) in mice. Cancer Biol. Ther., 2010, 9(2), 134-141.
Susumu, S.; Nagata, Y.; Ito, S.; Matsuo, M.; Valmori, D.; Yui, K.; Udono, H.; Kanematsu, T. Cross-presentation of NY-ESO-1 cytotoxic T lymphocyte epitope fused to human heat shock cognate protein 70 by dendritic cells. Cancer Sci., 2008, 99(1), 107-112.
Wang, X.Y.; Sun, X.; Chen, X.; Facciponte, J.; Repasky, E.A.; Kane, J.; Subjeck, J.R. Superior antitumor response induced by large stress protein chaperoned protein antigen compared with peptide antigen. J. Immunol., 2010, 184(11), 6309-6319.
Ge, W.; Hu, P.Z.; Huang, Y.; Wang, X.M.; Zhang, X.M.; Sun, Y.J.; Li, Z.S.; Si, S.Y.; Sui, Y.F. The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following different administration routes. Oncol. Rep., 2009, 22(4), 915-920.
Jager, D.; Filonenko, V.; Gout, I.; Frosina, D.; Eastlake-Wade, S.; Castelli, S.; Varga, Z.; Moch, H.; Chen, Y.T.; Busam, K.J.; Seil, I.; Old, L.J.; Nissan, A.; Frei, C.; Gure, A.O.; Knuth, A.; Jungbluth, A.A. NY-BR-1 is a differentiation antigen of the mammary gland. Appl. Immunohistochem. Mol. Morphol., 2007, 15(1), 77-83.
Theurillat, J.P.; Zürrer-Härdi, U.; Varga, Z.; Storz, M.; Probst-Hensch, N.M.; Seifert, B.; Fehr, M.K.; Fink, D.; Ferrone, S.; Pestalozzi, B.; Jungbluth, A.A.; Chen, Y.T.; Jäger, D.; Knuth, A.; Moch, H. NY-BR-1 protein expression in breast carcinoma: A mammary gland differentiation antigen as target for cancer immunotherapy. Cancer Immunol. Immunother., 2007, 56(11), 1723-1731.
Godoy, H.; Mhawech-Fauceglia, P.; Beck, A.; Miliotto, A.; Miller, A.; Lele, S.; Odunsi, K. Developmentally restricted differentiation antigens are targets for immunotherapy in epithelial ovarian carcinoma. Int. J. Gynecol. Pathol., 2013, 32(6), 536-540.
Metcalf, R.A.; Monabati, A.; Vyas, M.; Roncador, G.; Gualco, G.; Bacchi, C.E.; Younes, S.F.; Natkunam, Y.; Freud, A.G. Myeloid cell nuclear differentiation antigen is expressed in a subset of marginal zone lymphomas and is useful in the differential diagnosis with follicular lymphoma. Hum. Pathol., 2014, 45(8), 1730-1736.
Brichard, V.; Van Pel, A.; Wölfel, T.; Wölfel, C.; De Plaen, E.; Lethé, B.; Coulie, P.; Boon, T. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J. Exp. Med., 1993, 178(2), 489-495.
Bakker, A.B.; Schreurs, M.W.; Tafazzul, G.; de Boer, A.J.; Kawakami, Y.; Adema, G.J.; Figdor, C.G. Identification of a novel peptide derived from the melanocyte-specific gp100 antigen as the dominant epitope recognized by an HLA-A2.1-restricted anti-melanoma CTL line. Int. J. Cancer, 1995, 62(1), 97-102.
Coulie, P.G.; Brichard, V.; Van Pel, A.; Wölfel, T.; Schneider, J.; Traversari, C.; Mattei, S.; De Plaen, E.; Lurquin, C.; Szikora, J.P.; Renauld, J.C.; Boon, T. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J. Exp. Med., 1994, 180(1), 35-42.
Wang, W.; Epler, J.; Salazar, L.G.; Riddell, S.R. Recognition of breast cancer cells by CD8+ cytotoxic T-cell clones specific for NY-BR-1. Cancer Res., 2006, 66(13), 6826-6833.
Fisk, B.; Savary, C.; Hudson, J.M.; O’Brian, C.A.; Murray, J.L.; Wharton, J.T.; Ioannides, C.G. Changes in an HER-2 peptide upregulating HLA-A2 expression affect both con-formational epitopes and CTL recognition: implications for optimization of antigen presentation and tumor-specific CTL induction. J. Immunother. Emphasis Tumor Immunol., 1995, 18(4), 197-209.
Peoples, G.E.; Goedegebuure, P.S.; Smith, R.; Linehan, D.C.; Yoshino, I.; Eberlein, T.J. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc. Natl. Acad. Sci. USA, 1995, 92(2), 432-436.
Gravalos, C.; Jimeno, A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann. Oncol., 2008, 19(9), 1523-1529.
Richman, S.D.; Southward, K.; Chambers, P.; Cross, D.; Barrett, J.; Hemmings, G.; Taylor, M.; Wood, H.; Hutchins, G.; Foster, J.M.; Oumie, A.; Spink, K.G.; Brown, S.R.; Jones, M.; Kerr, D.; Handley, K.; Gray, R.; Seymour, M.; Quirke, P. HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials. J. Pathol., 2016, 238(4), 562-570.
Sotiropoulou, P.A.; Perez, S.A.; Voelter, V.; Echner, H.; Missitzis, I.; Tsavaris, N.B.; Papamichail, M.; Baxevanis, C.N. Natural CD8+ T-cell responses against MHC class I epitopes of the HER-2/ neu oncoprotein in patients with epithelial tumors. Cancer immunology, immunotherapy. CII, 2003, 52(12), 771-779.
Ladjemi, M.Z.; Jacot, W.; Pèlegrin, A.; Navarro-Teulon, I. [Anti-HER2 vaccines: The HER2 immunotargeting future?]. Pathol. Biol. (Paris), 2011, 59(3), 173-182.
Wölfel, T.; Hauer, M.; Schneider, J.; Serrano, M.; Wölfel, C.; Klehmann-Hieb, E.; De Plaen, E.; Hankeln, T.; Meyer zum Büschenfelde, K.H.; Beach, D.A. p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science, 1995, 269(5228), 1281-1284.
Robbins, P.F.; El-Gamil, M.; Li, Y.F.; Kawakami, Y.; Loftus, D.; Appella, E.; Rosenberg, S.A. A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J. Exp. Med., 1996, 183(3), 1185-1192.
Yanuck, M.; Carbone, D.P.; Pendleton, C.D.; Tsukui, T.; Winter, S.F.; Minna, J.D.; Berzofsky, J.A. A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T-cells. Cancer Res., 1993, 53(14), 3257-3261.
Coulie, P.G.; Lehmann, F.; Lethé, B.; Herman, J.; Lurquin, C.; Andrawiss, M.; Boon, T. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc. Natl. Acad. Sci. USA, 1995, 92(17), 7976-7980.
Avantaggiati, M.L.; Natoli, G.; Balsano, C.; Chirillo, P.; Artini, M.; De Marzio, E.; Collepardo, D.; Levrero, M. The hepatitis B virus (HBV) pX transactivates the c-fos promoter through multiple cis-acting elements. Oncogene, 1993, 8(6), 1567-1574.
Koutsky, L.A.; Ault, K.A.; Wheeler, C.M.; Brown, D.R.; Barr, E.; Alvarez, F.B.; Chiacchierini, L.M.; Jansen, K.U. A controlled trial of a human papillomavirus type 16 vaccine. N. Engl. J. Med., 2002, 347(21), 1645-1651.
van der Bruggen, P.; Traversari, C.; Chomez, P.; Lurquin, C.; De Plaen, E.; Van den Eynde, B.; Knuth, A.; Boon, T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991, 254(5038), 1643-1647.
Fiszer, D.; Kurpisz, M. Major histocompatibility complex expression on human, male germ cells: A review. Am. J. Reprod. Immunol., 1998, 40(3), 172-176.
Bart, J.; Groen, H.J.; van der Graaf, W.T.; Hollema, H.; Hendrikse, N.H.; Vaalburg, W.; Sleijfer, D.T.; de Vries, E.G. An oncological view on the blood-testis barrier. Lancet Oncol., 2002, 3(6), 357-363.
Van Der Bruggen, P.; Zhang, Y.; Chaux, P.; Stroobant, V.; Panichelli, C.; Schultz, E.S.; Chapiro, J.; Van Den Eynde, B.J.; Brasseur, F.; Boon, T. Tumor-specific shared antigenic peptides recognized by human T cells. Immunol. Rev., 2002, 188, 51-64.
Golovastova, M.O.; Bazhin, A.V.; Philippov, P.P. Cancer-retina antigens -- a new group of tumor antigens. Biochemistry (Mosc.), 2014, 79(8), 733-739.
Golovastova, M.O.; Korolev, D.O.; Tsoy, L.V.; Varshavsky, V.A.; Xu, W.H.; Vinarov, A.Z.; Zernii, E.Y.; Philippov, P.P.; Zamyatnin, A.A., Jr Biomarkers of renal tumors: The current state and clinical perspectives. Curr. Urol. Rep., 2017, 18(1), 3.
Huh, G.S.; Boulanger, L.M.; Du, H.; Riquelme, P.A.; Brotz, T.M.; Shatz, C.J. Functional requirement for class I MHC in CNS development and plasticity. Science, 2000, 290(5499), 2155-2159.
Engelhardt, B.; Coisne, C. Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle. Fluids Barriers CNS, 2011, 8(1), 4.
Sallusto, F.; Impellizzieri, D.; Basso, C.; Laroni, A.; Uccelli, A.; Lanzavecchia, A.; Engelhardt, B. T-cell trafficking in the central nervous system. Immunol. Rev., 2012, 248(1), 216-227.
Jacobson, D.M.; Thirkill, C.E.; Tipping, S.J. A clinical triad to diagnose paraneoplastic retinopathy. Ann. Neurol., 1990, 28(2), 162-167.
Rosenblum, M.K. Paraneoplasia and autoimmunologic injury of the nervous system: The anti-Hu syndrome. Brain Pathol., 1993, 3(3), 199-212.
Giometto, B.; Taraloto, B.; Graus, F. Autoimmunity in paraneoplastic neurological syndromes. Brain Pathol., 1999, 9(2), 261-273.
Bazhin, A.V.; Savchenko, M.S.; Shifrina, O.N.; Demoura, S.A.; Chikina, S.Y.; Jaques, G.; Kogan, E.A.; Chuchalin, A.G.; Philippov, P.P. Recoverin as a paraneoplastic antigen in lung cancer: the occurrence of anti-recoverin autoantibodies in sera and recoverin in tumors. Lung Cancer, 2004, 44(2), 193-198.
Eichmüller, S.B.; Bazhin, A.V. Onconeural versus paraneoplastic antigens? Curr. Med. Chem., 2007, 14(23), 2489-2494.
Bazhin, A.V.; Shifrina, O.N.; Savchenko, M.S.; Tikhomirova, N.K.; Goncharskaia, M.A.; Gorbunova, V.A.; Senin, I.I.; Chuchalin, A.G.; Philippov, P.P. Low titre autoantibodies against recoverin in sera of patients with small cell lung cancer but without a loss of vision. Lung Cancer, 2001, 34(1), 99-104.
Bazhin, A.V.; Schadendorf, D.; Philippov, P.P.; Eichmüller, S.B. Recoverin as a cancer-retina antigen. Cancer Immunol. Immunother., 2007, 56(1), 110-116.
Gromadzka, G.; Karlińska, A.G.; Łysiak, Z.; Błażejewska-Hyżorek, B.; Litwin, T.; Członkowska, A. Positivity of serum “classical” onconeural antibodies in a series of 2063 consecutive patients with suspicion of paraneoplastic neurological syndrome. J. Neuroimmunol., 2013, 259(1-2), 75-80.
Dalmau, J.; Furneaux, H.M.; Cordon-Cardo, C.; Posner, J.B. The expression of the Hu (paraneoplastic encephalomyelitis/sensory neuronopathy) antigen in human normal and tumor tissues. Am. J. Pathol., 1992, 141(4), 881-886.
Luque, F.A.; Furneaux, H.M.; Ferziger, R.; Rosenblum, M.K.; Wray, S.H.; Schold, S.C., Jr; Glantz, M.J.; Jaeckle, K.A.; Biran, H.; Lesser, M. Anti-Ri: An antibody associated with paraneoplastic opsoclonus and breast cancer. Ann. Neurol., 1991, 29(3), 241-251.
Peterson, K.; Rosenblum, M.K.; Kotanides, H.; Posner, J.B. Paraneoplastic cerebellar degeneration. I. A clinical analysis of 55 anti-Yo antibody-positive patients. Neurology, 1992, 42(10), 1931-1937.
Polans, A.S.; Buczyłko, J.; Crabb, J.; Palczewski, K. A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy. J. Cell Biol., 1991, 112(5), 981-989.
Maeda, A.; Ohguro, H.; Maeda, T.; Wada, I.; Sato, N.; Kuroki, Y.; Nakagawa, T. Aberrant expression of photoreceptor-specific calcium-binding protein (recoverin) in cancer cell lines. Cancer Res., 2000, 60(7), 1914-1920.
Golovastova, M.O.; Tsoy, L.V.; Bocharnikova, A.V.; Korolev, D.O.; Gancharova, O.S.; Alekseeva, E.A.; Kuznetsova, E.B.; Savvateeva, L.V.; Skorikova, E.E.; Strelnikov, V.V.; Varshavsky, V.A.; Vinarov, A.Z.; Nikolenko, V.N.; Glybochko, P.V.; Zernii, E.Y.; Zamyatnin, A.A., Jr; Bazhin, A.V.; Philippov, P.P. The cancer-retina antigen recoverin as a potential biomarker for renal tumors. Tumour Biol., 2016, 37(7), 9899-9907.
Bazhin, A.V.; Schadendorf, D.; Willner, N.; De Smet, C.; Heinzelmann, A.; Tikhomirova, N.K.; Umansky, V.; Philippov, P.P.; Eichmüller, S.B. Photoreceptor proteins as cancer-retina antigens. Int. J. Cancer, 2007, 120(6), 1268-1276.
Matsuo, S.; Ohguro, H.; Ohguro, I.; Nakazawa, M. Clinicopathological roles of aberrantly expressed recoverin in malignant tumor cells. Ophthalmic Res., 2010, 43(3), 139-144.
Ohguro, H.; Odagiri, H.; Miyagawa, Y.; Ohguro, I.; Sasaki, M.; Nakazawa, M. Clinicopathological features of gastric cancer cases and aberrantly expressed recoverin. Tohoku J. Exp. Med., 2004, 202(3), 213-219.
Weber, J.; Salgaller, M.; Samid, D.; Johnson, B.; Herlyn, M.; Lassam, N.; Treisman, J.; Rosenberg, S.A. Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2′-deoxycytidine. Cancer Res., 1994, 54(7), 1766-1771.
Bazhin, A.V.; De Smet, C.; Golovastova, M.O.; Schmidt, J.; Philippov, P.P. Aberrant demethylation of the recoverin gene is involved in the aberrant expression of recoverin in cancer cells. Exp. Dermatol., 2010, 19(11), 1023-1025.
Zhao, R.Y.; Mifsud, N.A.; Xiao, K.; Chan, K.F.; Oveissi, S.; Jackson, H.M.; Dimopoulos, N.; Guillaume, P.; Knights, A.J.; Lowen, T.; Robson, N.C.; Russell, S.E.; Scotet, E.; Davis, I.D.; Maraskovsky, E.; Cebon, J.; Luescher, I.F.; Chen, W. A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by dendritic cells from soluble tumor antigen. PLoS One, 2012, 7(9), e44707.
Ciupitu, A.M.; Petersson, M.; O’Donnell, C.L.; Williams, K.; Jindal, S.; Kiessling, R.; Welsh, R.M. Immunization with a lymphocytic choriomeningitis virus peptide mixed with heat shock protein 70 results in protective antiviral immunity and specific cytotoxic T lymphocytes. J. Exp. Med., 1998, 187(5), 685-691.
Moroi, Y.; Mayhew, M.; Trcka, J.; Hoe, M.H.; Takechi, Y.; Hartl, F.U.; Rothman, J.E.; Houghton, A.N. Induction of cellular immunity by immunization with novel hybrid peptides complexed to heat shock protein 70. Proc. Natl. Acad. Sci. USA, 2000, 97(7), 3485-3490.
Flechtner, J.B.; Cohane, K.P.; Mehta, S.; Slusarewicz, P.; Leonard, A.K.; Barber, B.H.; Levey, D.L.; Andjelic, S. High-affinity interactions between peptides and heat shock protein 70 augment CD8+ T lymphocyte immune responses. J. Immunol., 2006, 177(2), 1017-1027.
Javid, B.; MacAry, P.A.; Oehlmann, W.; Singh, M.; Lehner, P.J. Peptides complexed with the protein HSP70 generate efficient human cytolytic T-lymphocyte responses. Biochem. Soc. Trans., 2004, 32(Pt 4), 622-625.
Murshid, A.; Gong, J.; Stevenson, M.A.; Calderwood, S.K. Heat shock proteins and cancer vaccines: Developments in the past decade and chaperoning in the decade to come. Expert Rev. Vaccines, 2011, 10(11), 1553-1568.
Bystryn, J.C.; Zeleniuch-Jacquotte, A.; Oratz, R.; Shapiro, R.L.; Harris, M.N.; Roses, D.F. Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine. Clin. Cancer Res., 2001, 7(7), 1882-1887.
Young, M.D.; Gooch, W.M., III; Zuckerman, A.J.; Du, W.; Dickson, B.; Maddrey, W.C. Comparison of a triple antigen and a single antigen recombinant vaccine for adult hepatitis B vaccination. J. Med. Virol., 2001, 64(3), 290-298.
Willadsen, P. Antigen cocktails: Valid hypothesis or unsub-stantiated hope? Trends Parasitol., 2008, 24(4), 164-167.
Suzue, K.; Zhou, X.; Eisen, H.N.; Young, R.A. Heat shock fusion proteins as vehicles for antigen delivery into the major histocompatibility complex class I presentation pathway. Proc. Natl. Acad. Sci. USA, 1997, 94(24), 13146-13151.
Moré, S.; Breloer, M.; Fleischer, B.; von Bonin, A. Activation of cytotoxic T cells in vitro by recombinant gp96 fusion proteins irrespective of the ‘fused’ antigenic peptide sequence. Immunol. Lett., 1999, 69(2), 275-282.
Udono, H.; Yamano, T.; Kawabata, Y.; Ueda, M.; Yui, K. Generation of cytotoxic T lymphocytes by MHC class I ligands fused to heat shock cognate protein 70. Int. Immunol., 2001, 13(10), 1233-1242.
Mizukami, S.; Kajiwara, C.; Ishikawa, H.; Katayama, I.; Yui, K.; Udono, H. Both CD4+ and CD8+ T cell epitopes fused to heat shock cognate protein 70 (hsc70) can function to eradicate tumors. Cancer Sci., 2008, 99(5), 1008-1015.
Takemoto, S.; Nishikawa, M.; Guan, X.; Ohno, Y.; Yata, T.; Takakura, Y. Enhanced generation of cytotoxic T lymphocytes by heat shock protein 70 fusion proteins harboring both CD8(+) T cell and CD4(+) T cell epitopes. Mol. Pharm., 2010, 7(5), 1715-1723.
Mo, X.Y.; Cascio, P.; Lemerise, K.; Goldberg, A.L.; Rock, K. Distinct proteolytic processes generate the C and N termini of MHC class I-binding peptides. J. Immunol., 1999, 163(11), 5851-5859.
Takemoto, S.; Nishikawa, M.; Otsuki, T.; Yamaoka, A.; Maeda, K.; Ota, A.; Takakura, Y. Enhanced generation of cytotoxic T lymphocytes by increased cytosolic delivery of MHC class I epitope fused to mouse heat shock protein 70 via polyhistidine conjugation. J. Control. Release, 2009, 135(1), 11-18.
Germeau, C.; Ma, W.; Schiavetti, F.; Lurquin, C.; Henry, E.; Vigneron, N.; Brasseur, F. High frequency of antitumor T cells in the blood of melanoma patients before and after vaccina-tion with tumor antigens. J. Exp. Med., 2005, 201(2), 241-248.

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Year: 2019
Page: [427 - 445]
Pages: 19
DOI: 10.2174/0929867325666180129100015
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